Featured Research

from universities, journals, and other organizations

Potential new use found for cancer drug in gene therapy for blood disorders

Date:

June 26, 2014

Source:

Scripps Research Institute

Summary:

Scientists working to make gene therapy a reality have solved a major hurdle: how to bypass a blood stem cell’s natural defenses and efficiently insert disease-fighting genes into the cell’s genome. These findings could lead to more effective and affordable long-term treatments for blood cell disorders in which mutations in the DNA cause abnormal cell functions, such as in leukemia and sickle cell anemia.

Related Articles

In a new study led by Associate Professor Bruce Torbett at The Scripps Research Institute (TSRI), a team of researchers report that the drug rapamycin, which is commonly used to slow cancer growth and prevent organ rejection, enables delivery of a therapeutic dose of genes to blood stem cells while preserving stem cell function.

These findings, published recently online ahead of print by the journal Blood, could lead to more effective and affordable long-term treatments for blood cell disorders in which mutations in the DNA cause abnormal cell functions, such as in leukemia and sickle cell anemia.

Improving Gene Delivery to Blood Stem Cells

Viruses infect the body by inserting their own genetic material into human cells. In gene therapy, however, scientists have developed "gutted" viruses, such as the human immunodeficiency virus (HIV), to produce what are called "viral vectors." Viral vectors carry therapeutic genes into cells without causing viral disease. Torbett and other scientists have shown that HIV vectors can deliver genes to blood stem cells.

For a disease such as leukemia or leukodystrophy, where mutations in the DNA cause abnormal cell function, efficiently targeting the stem cells that produce these blood cells could be a successful approach to halting the disease and prompting the body to produce healthy blood cells.

"If you produce a genetic modification in your blood stem cells when you are five years old, these changes are lifelong," said Torbett. Furthermore, the gene-modified stem cells can develop into many types of cells that travel throughout the body to provide therapeutic effects.

However, because cells have adapted defense mechanisms to overcome disease-causing viruses, engineered viral vectors can be prevented from efficiently delivering genes. Torbett said that when scientists extract blood stem cells from the body for gene therapy, HIV viral vectors are usually able to deliver genes to only 30 to 40 percent of them. For leukemia, leukodystrophy or genetic diseases where treatment requires a reasonable number of healthy cells coming from stem cells, this number may be too low for therapeutic purposes.

This limitation prompted Torbett and his team, including TSRI graduate student Cathy Wang, the first author of the study, to test whether rapamycin could improve delivery of a gene to blood stem cells. Rapamycin was selected for evaluation based on its ability to control virus entry and slow cell growth.

The researchers began by isolating stem cells from cord blood samples. They exposed the blood stem cells to rapamycin and HIV vectors engineered to deliver a gene for a green florescent protein, which causes cells to glow. This fluorescence provided a visual marker that helped the researchers track gene delivery.

The researchers saw a big difference in both mouse and human stem cells treated with rapamycin, where therapeutic genes were inserted into up to 80 percent of cells. This property had never been connected to rapamycin before.

Helping Blood Stem Cells Survive

The researchers also found that rapamycin can keep stem cells from differentiating as quickly when taken out of the body for gene therapy. This is important because scientists need time to work on extracted blood stem cells -- yet once these cells leave the body, they begin to differentiate if manipulated into other types of blood cells and lose the ability to remain as stem cells and pass on therapeutic genes.

"We wanted to make sure the conditions we will use preserve stem cells, so if we transplant them back into our animal models, they act just like the original stem cells," said Torbett. "We showed that in two sets of animal models, stem cells remain and produce gene-modified cells."

The researchers hope these methods could someday be useful in the clinic. "Our methods could reduce costs and the amount of preparation that goes into modifying blood stem cells using viral vector gene therapy," said Wang. "It would make gene therapy accessible to a lot more patients."

She said the next steps are to carry out preclinical studies using rapamycin with stem cells in other animal models and then see if the method is safe and effective in humans. The team is also working to delineate the dual pathways of rapamycin's method of action in blood stem cells.

Scripps Research Institute. "Potential new use found for cancer drug in gene therapy for blood disorders." ScienceDaily. ScienceDaily, 26 June 2014. <www.sciencedaily.com/releases/2014/06/140626160845.htm>.

Scripps Research Institute. (2014, June 26). Potential new use found for cancer drug in gene therapy for blood disorders. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2014/06/140626160845.htm

Scripps Research Institute. "Potential new use found for cancer drug in gene therapy for blood disorders." ScienceDaily. www.sciencedaily.com/releases/2014/06/140626160845.htm (accessed March 3, 2015).

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Pediatric otolaryngologists and surgeons are concerned with parents getting the wrong message regarding the safety/desirability of letting babies and young children eat peanuts to prevent them from ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Feb. 26, 2015 — It's almost inevitable that we'll develop mutations associated with leukemia as we age, according to new research. These mutations are more common than previously thought and their numbers ... full story

Oct. 8, 2014 — Gene therapy using a modified delivery system, or vector, can restore the immune systems of children with X-linked severe combined immunodeficiency (SCID-X1), a rare, life-threatening inherited ... full story

Aug. 5, 2014 — A major hurdle in gene therapy is the efficient integration of a corrected gene into a patient's genome without mutating off-target sites. In a new paper, scientists explain having used ... full story

Mar. 27, 2012 — Scientists have designed what appears to be a powerful gene therapy strategy that can treat both beta-thalassemia disease and sickle cell anemia. They have also developed a test to predict patient ... full story

Dec. 7, 2011 — Researchers have developed a way to use patients' own cells to potentially cure sickle cell disease and many other disorders caused by mutations in a gene that helps produce blood ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.